The long term objective of this project is to investigate the efficacy of hyperthermia as an adjuvant to radiation therapy or chemotherapy in the treatment of cancer. This proposal addresses two specific areas: (1) development and testing of improved techniques for controlling temperature distributions in superficial and deep-seated tumors, and (2) investigations of the interactions between hyperthermia and brachytherapy and between hyperthermia and certain chemotherapeutic agents. Major specific aims include the following: (1) new refinements of the interstitial microwave antenna array hyperthermia (IMAAH) system to incorporate features such as variable phase control, air cooling of antennas, and new antenna designs, together with appropriate evaluations of the refined system in animals and in clinical tumors. (2) The continued evaluation of the IMAAH system's effectiveness in heating deep-seated tumors that are difficult to heat by non-invasive systems, especially those in the abdomen and pelvic regions. (3) The use of a transplantable murine mammary tumor (MTG-B) to investigate interactions between brachytherapy and hyperthermia. These studies will evaluate the effect of parameters important to clinical protocols such as (a) sequencing, (b) time-dose relationships and (c) the influence of brachytherapy on the magnitude and kinetics of thermotolerance. In these studies tumor regrowth delay, tumor control (TCD50), and cell colony-forming units (CFU) in vitro following treatment in tumors will be used as analytical endpoints. (4) Examination of the effects of hyperthermia in combination with platinum chemotherapy in MTG-B, to be followed by pilot clinical studies of IMAAH and ultrasound induced hyperthermia in combination with platinum chemotherapy in superficial tumors so as to gain information for treating deep- seated tumors with this combined modality approach. Platinum levels will be measured in MTG-B and in the clinical tumors using atomic absorption spectrometry (AAS). Therefore, the studies proposed will not only continue to develop new techniques for providing better temperature distributions throughout the tumor and surrounding normal tissue, but will also exploit the controlled temperatures produced by these systems to obtain crucial information to further our understanding of the combination of brachytherapy or chemotherapy with hyperthermia in the treatment of cancer.